The Ig gene superfamily, described by Williams et al., Annu. Rev. Immunol., 88:381-405 (1988), encompasses a large family of genes that are presumed to have evolved from a common precursor. Many of the Ig superfamily members are involved in cell-cell adhesion and signal transduction. In addition, many of the cell-surface molecules which regulate immune responses contain conserved structural features similar to those found in immunoglobulin (Ig). While most members of the Ig gene superfamily contain multiple linearly-assembled Ig-like domains, several proteins have been identified that contain single Ig-like domains.
Single Ig-like domain proteins that are known or assumed to be involved in cell-cell adhesion include: CD8.alpha. (Littman et al., Cell 40:237 (1985)), CD8.beta. (Johnson et al., Nature 323:74 (1986)), CD7 (Aruffo et al., EMBO J. 6:3313 (1987)), Thy-1 (Williams et al., Science 216:696 (1982)), CD28 (Aruffo et al., Proc. Natl. Acad. Sci. USA 84:8573 (1987)), CTLA-4 (Brunet et al., Nature 328:267 (1987)) and Po which is a structural protein of the peripheral myelin sheath (Lemke et al., Cell 40:501 (1985)). In addition, other single Ig-domain containing proteins associate with the antigen receptors of B and T lymphocytes, forming multimeric signal-transducing complexes. These include: CD3 .gamma., .delta. and .epsilon. chains (Gold et al., Nature 321:431-434 (1986); van den Elsen et al., Nature 312:413-418 (1984)), CD79.beta. (Hermanson et al., Proc. Natl. Acad. Sci., USA 85:6890 (1988)), and CD79.alpha. (Sakaguchi et al., EMBO J. 7:3457-3464 (1988)).
Two proteins containing single Ig-like domains found on lymphocytes are preferentially associated with cellular activation and are known to be involved in mediating cell-cell interactions. CD28 is expressed much more on activated than nonactivated T and B lymphocytes (Turka et al., J. Immunol. 144:1646 (1990)), and CTLA-4 is expressed mostly, if not exclusively, by activated T and B lymphocytes (Brunet et al., Nature 328:267 (1987); Harper et al., J. Immunol. 147:1037-1044 (1991)). The role of CD28 as a T cell receptor for the CD80 molecule expressed by activated B cells has been recently identified (Linsley et al., Proc. Natl. Acad. Sci. USA 87:5031-503 (1990); Freeman et al., J. Immunol. 143:2714-2722 (1989)), as has a similar role for CTLA-4 (Linsley et al., J. Exp. Med. 174:561-569 (1991)). As with CD28 and CD80, most of the Ig-like domain-containing receptors interact with members of the Ig superfamily present on other cells.
It is an object of the invention to provide a new member of the Ig gene superfamily. Another object of the invention is to provide a protein that is found predominantly on lymphoid tissue. Yet another object of the invention is to provide a protein that contains an extracellular single Ig-like domain. Yet another object of the invention is to provide a nucleic acid encoding the protein or a biologically active portion of the protein. Another object of the invention is to provide nucleic acid probes for identifying the protein or homologs thereof. Yet another object of the invention is to provide an antigen that is present on activated lymphocytes, but absent on inactive lymphocytes and most other cell types.